METHODS OF TREATMENT USING SIRT MODULATORS AND COMPOSITIONS CONTAINING SIRT1 MODULATORS

• US 20100210692A1
• Filed: 03/28/2008
• Published: 08/19/2010
• Est. Priority Date: 03/28/2007
• Status: Abandoned Application

• Current Assignee: Trustees of Boston University
• Original Assignee: Trustees of Boston University
• Inventors: Wang, Hong, Qiang, Li, Farmer, Stephen R.
• Application Number:
  US12/593,082
• Publication Number:
  US 20100210692A1
• Time in Patent Office: Days
• US Class Current: 514/342
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/40 having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
• CPC Class Codes: A61K 31/4439 containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole nicotine A61K31/465
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system

Abstract

Methods of treatment using SIR1 modulators and compositions containing SIRT1 modulators are described. Combinations of a SIRT1 modulator and a second agent, and uses of such combinations, are also described.

Claims

1. A method of treating a disorder in a subject, the method comprising administering a SIRT1 inhibitor and a PPARγ

agonist to the subject.

2. The method of claim 1, wherein the disorder is a metabolic disorder, a neoplastic disorder, dyslipidemia, arteriosclerosis, inflammation, a cardiovascular disorder, or ischemia.

3. The method of claim 1, wherein the SIRT1 inhibitor is a compound of formula (XI) below:

4. The method of claim 3, wherein the compound is 6-Chloro-2,3,4,9-tetrahydro-1H-carbazole-1-carboxylic acid amide.

5. The method claim 3, comprising a composition comprising at least a 60% enantiomeric excess of the enantiomer of formula (XI) having an optical rotation of −

14.1 (c−

0.33 DCM);

6. The method of claim 3, comprising a composition comprising at least a 60% enantiomeric excess of the enantiomer of formula (XI) having an optical rotation of −

14.1 (c=0.33 DCM).

7. The method of claim 3, wherein the PPARγ

agonist is a thiazolidinedione (TZD).

8. The method of claim 7, wherein the TZD comprises rosiglitazone, pioglitazone, troglitazone, or ciglitazone.

9. The method of claim 1, wherein the PPARγ

agonist is a non-thiazolidinedione (non-TZD).

10. The method of claim 9, wherein the non-TZD comprises aleglitazar, muraglitazar, tesaglitazar, 15-deoxy-Δ

_12,14-prostaglandin J₂ (15d-PGJ₂), GW1929, GW7845, RWJ-348260, AK109, mono-2-ethyhexyl phthalate, GI262570, an eicosanoid, or a tetrahydroisoquinoline PPARγ

agonist.

11. A composition comprising a SIRT1 inhibitor and a PPARγ

agonist.

12. The composition of claim 11, wherein the SIRT1 inhibitor is a compound of formula (XI) below:

13. The composition of claim 12, wherein the compound. 6-Chloro-2,3,4,9-tetrahydro-1H-carbazole-1-carboxylic acid amide.

14. The composition of claim 12, comprising a composition comprising at least a 60% enantiomeric excess of the enantiomer of formula (XI) having an optical rotation of −

14A (c=0.33 DCM).

15. The composition of claim 12, comprising a composition comprising at least a 90% enantiomeric excess of the enantiomer of formula (XI) having an optical rotation of −

14A (c=0.33 DCM).

16. The composition of claim 11, wherein the PPARγ

agonist is a thiazolidinedione (TZD).

17. The composition of claim 16, wherein the TZD comprises rosiglitazone, pioglitazone, troglitazone, or ciglitazone.

18. The composition of claim 11, wherein the PPARγ

agonist is a non-thiazolidinedione (non-TZD).

19. The composition of claim 18, wherein the non-TZD comprises aleglitazar, muraglitazar, tesaglitazar, 15-deoxy-Δ

_12,14-prostaglandin J₂ (15d-PGJ₂), GW1929, GW7845, RWJ-348260, AK109, mono-2-ethyhexyl phthalate, GI262570, an eicosanoid, or a tetrahydroisoquinoline PPARγ

agonist.